Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
EMBO J
1993 Oct 01;1210:3809-15. doi: 10.1002/j.1460-2075.1993.tb06059.x.
Show Gene links
Show Anatomy links
Charged amino acids required for signal transduction by the m3 muscarinic acetylcholine receptor.
Kunkel MT
,
Peralta EG
.
???displayArticle.abstract???
The five muscarinic acetylcholine receptor (mAChR) subtypes, termed m1-m5, transduce agonist signals across the plasma membrane by activating guanine nucleotide binding (G) proteins. The large cytoplasmic domain joining the fifth and sixth transmembrane segments of mAChRs plays a critical role in controlling the specificity of G protein coupling. In this study, we determined which sequences within this domain are required for activation of signaling by the m3 mAChR. By measuring the ability of normal and mutant m3 mAChRs to couple to the G protein pathway leading to activation of phospholipase C and Ca(2+)-dependent chloride currents in RNA-injected Xenopus oocytes, we found that two clusters of charged residues near the fifth and sixth transmembrane segments were required for normal signaling; furthermore, the position of these sequences was critical for their function. Finally, analysis of deletion mutant m3 mAChRs confirmed the importance of these sequences; receptors containing as few as 22 out of 239 amino acids of the cytoplasmic domain were fully active in signaling if they included the critical charged residues. Sequence comparisons suggest that similar charged sequences may be required for signal transduction by many G protein-coupled receptors.
Ashkenazi,
Functionally distinct G proteins selectively couple different receptors to PI hydrolysis in the same cell.
1989, Pubmed
Ashkenazi,
Functionally distinct G proteins selectively couple different receptors to PI hydrolysis in the same cell.
1989,
Pubmed
Berridge,
Inositol trisphosphate and calcium signalling.
1993,
Pubmed
Berstein,
Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-beta 1.
1992,
Pubmed
Birnbaumer,
Receptor-to-effector signaling through G proteins: roles for beta gamma dimers as well as alpha subunits.
1992,
Pubmed
Cotecchia,
Regions of the alpha 1-adrenergic receptor involved in coupling to phosphatidylinositol hydrolysis and enhanced sensitivity of biological function.
1990,
Pubmed
Dalman,
Two peptides from the alpha 2A-adrenergic receptor alter receptor G protein coupling by distinct mechanisms.
1991,
Pubmed
Dell'Acqua,
Transfected m2 muscarinic acetylcholine receptors couple to G alpha i2 and G alpha i3 in Chinese hamster ovary cells. Activation and desensitization of the phospholipase C signaling pathway.
1993,
Pubmed
England,
A chimeric D2 dopamine/m1 muscarinic receptor with D2 binding specificity mobilizes intracellular calcium in response to dopamine.
1991,
Pubmed
Fujimoto,
Mast cell degranulating (MCD) peptide and its optical isomer activate GTP binding protein in rat mast cells.
1991,
Pubmed
Gutowski,
Antibodies to the alpha q subfamily of guanine nucleotide-binding regulatory protein alpha subunits attenuate activation of phosphatidylinositol 4,5-bisphosphate hydrolysis by hormones.
1991,
Pubmed
Higashijima,
Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins).
1988,
Pubmed
Higashijima,
Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines. Mechanism and structural determinants of activity.
1990,
Pubmed
Higashijima,
Conformational change of mastoparan from wasp venom on binding with phospholipid membrane.
1983,
Pubmed
Kaziro,
Structure and function of signal-transducing GTP-binding proteins.
1991,
Pubmed
Kjelsberg,
Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation.
1992,
Pubmed
Kobilka,
Chimeric alpha 2-,beta 2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity.
1988,
Pubmed
Kubo,
Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling.
1988,
Pubmed
,
Xenbase
Kunkel,
Rapid and efficient site-specific mutagenesis without phenotypic selection.
1987,
Pubmed
Lechleiter,
Distinct sequence elements control the specificity of G protein activation by muscarinic acetylcholine receptor subtypes.
1990,
Pubmed
,
Xenbase
Lechleiter,
Subcellular patterns of calcium release determined by G protein-specific residues of muscarinic receptors.
1991,
Pubmed
,
Xenbase
Melton,
Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter.
1984,
Pubmed
Munson,
Ligand: a versatile computerized approach for characterization of ligand-binding systems.
1980,
Pubmed
Okamoto,
A simple structure encodes G protein-activating function of the IGF-II/mannose 6-phosphate receptor.
1990,
Pubmed
Okamoto,
Detection of G protein-activator regions in M4 subtype muscarinic, cholinergic, and alpha 2-adrenergic receptors based upon characteristics in primary structure.
1992,
Pubmed
Oppi,
Attenuation of GTPase activity of recombinant G(o) alpha by peptides representing sequence permutations of mastoparan.
1992,
Pubmed
Peralta,
Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors.
1987,
Pubmed
Peralta,
Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes.
1988,
Pubmed
Tabor,
DNA sequence analysis with a modified bacteriophage T7 DNA polymerase.
1987,
Pubmed
Taylor,
Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins.
1991,
Pubmed
Voss,
Amphipathic alpha-helical structure does not predict the ability of receptor-derived synthetic peptides to interact with guanine nucleotide-binding regulatory proteins.
1993,
Pubmed
Wess,
Identification of a small intracellular region of the muscarinic m3 receptor as a determinant of selective coupling to PI turnover.
1989,
Pubmed
Wong,
Chimeric muscarinic cholinergic: beta-adrenergic receptors that activate Gs in response to muscarinic agonists.
1990,
Pubmed
